This proposal to study the control of ion fluxes across the membranes of sarcoplasmic reticulum (SR) and sarcolemma is intended to provide basic information regarding the pathogenesis and therapy of heart failure and cardiac arrhythmias. Specific projects will examine the effects of fatty acids and fatty acid derivatives on Ca fluxes across the SR, effects of nucleotides on Ca transport and release by the SR, mechanisms of caffeine effects on the SR, and the possible role of protein-protein interactions in the control of Ca influx and efflux in the SR. These and other projects would allow the continuation of studies, now underway, that are directed to aiding in the development of a systematic description of normal and abnormal mechanisms controlling transmembrane ion fluxes in the heart.